INTRODUCTION AND OBJECTIVES: With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options. MATERIALS AND METHODS: This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months. RESULTS: Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009). CONCLUSIONS: Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis. GOV REGISTRATION: NCT04895943.

• MeSH
• bariatrická chirurgie * MeSH
• časové faktory MeSH
• design vybavení MeSH
• dospělí MeSH
• elastografie MeSH
• hmotnostní úbytek MeSH
• jaterní cirhóza * etiologie   diagnostické zobrazování   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nealkoholová steatóza jater * diagnostické zobrazování   diagnóza   etiologie   MeSH
• obezita * komplikace   chirurgie   diagnóza   MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• výsledek terapie MeSH
• žaludeční balónek * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH

INTRODUCTION: A variable proportion of non-responders to cardiac resynchronization therapy (CRT) warrants the search for new approaches to optimize the position of the left ventricular (LV) lead and the CRT device programming. CineECG is a novel ECG modality proposed for the spatial visualization and quantification of myocardial depolarization and repolarization sequences. OBJECTIVE: The present study aimed to evaluate CineECG-derived parameters in different pacing modes and to test their associations with acute hemodynamic responses in CRT patients. METHODS AND RESULTS: CineECG was used to construct the average electrical path within the cardiac anatomy from the 12-lead ECG. CineECG and LV dP/dt max were tested in 15 patients with nonischemic dilated cardiomyopathy and left bundle branch block (QRS: 170 ± 17 ms; LVEF: 26 ± 5.5%) under pacing protocols with different LV lead localizations. The CineECG-derived path directions were computed for the QRS and ST-T intervals for the anteroposterior (Xh), interventricular (Yh), and apicobasal (Zh) axes. In a multivariate linear regression analysis with adjustment for the pacing protocol type, the ST-T path direction Yh was independently associated with the increase in dP/dt max during CRT, [regression coefficient 639.4 (95% confidence interval: 187.9-1090.9), p = 0.006]. In ROC curve analysis, the ST-T path direction Yh was associated with the achievement of a 10% increase in dP/dt max (AUC: 0.779, p = 0.002) with the optimal cut-off > 0.084 (left-to-right direction) with sensitivity 0.67 and specificity 0.92. CONCLUSION: The acute hemodynamic response in CRT patients was associated with specific CineECG repolarization sequence parameters, warranting their further testing as potential predictors of clinical outcomes.

• MeSH
• akční potenciály MeSH
• blokáda Tawarova raménka * patofyziologie   terapie   diagnóza   MeSH
• časové faktory MeSH
• dilatační kardiomyopatie patofyziologie   terapie   diagnóza   MeSH
• elektrokardiografie * MeSH
• funkce levé komory srdeční * MeSH
• hemodynamika * MeSH
• lidé středního věku MeSH
• lidé MeSH
• prediktivní hodnota testů * MeSH
• prostředky srdeční resynchronizační terapie MeSH
• senioři MeSH
• srdeční frekvence MeSH
• srdeční resynchronizační terapie * MeSH
• srdeční selhání patofyziologie   terapie   diagnóza   MeSH
• tepový objem MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Increased lung cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately and by multiple quantitative bias analyses, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased the direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung cancer risk in the multiple bias analysis. Lung cancer risks remained increased for lower SES groups, with higher risks in men (fourth vs. first [highest] SES quartile: CDE, 1.50 [SI, 1.32, 1.69]) than women (CDE: 1.20 [SI: 1.01, 1.45]). Natural direct effects were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.

• MeSH
• analýza mediace * MeSH
• dospělí MeSH
• kouření * epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• nádory plic * epidemiologie   MeSH
• odds ratio MeSH
• rizikové faktory MeSH
• senioři MeSH
• společenská třída * MeSH
• studie případů a kontrol MeSH
• zkreslení výsledků (epidemiologie) * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

• MeSH
• alfa-galaktosidasa * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• enzymová substituční terapie * metody   MeSH
• Fabryho nemoc * farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• polyethylenglykoly aplikace a dávkování   MeSH
• rekombinantní proteiny * aplikace a dávkování   terapeutické užití   MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• sfingolipidy krev   MeSH
• trihexosylceramidy krev   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

The largest obstacle in the promotion of biopesticides is the existence of counterfeit products available in the market. Identification and quantification of antagonistic organisms in biopesticide products are the key to the reduction of spurious microbial pesticides. In this study, we have developed a simple, sensitive, isothermal-based colourimetric assay for specific detection of Bacillus subtilis from the biopesticide formulations and soil samples. A region specific to B. subtilis which codes for shikimate dehydrogenase was identified through in silico analysis. We employed conventional PCR, loop-mediated isothermal amplification (LAMP), recombinase polymerase amplification (RPA), and qPCR for specific detection of B. subtilis in soil samples and biopesticide formulations. Specificity tests showed that the PCR primers amplified an amplicon of 521 bp in four strains of B. subtilis only, and no amplification was found in negative control samples. Similarly, the LAMP assay showed sky blue colour in all four strains of B. subtilis and violet colour in negative control samples. Whereas in the RPA assay, upon the addition of SYBR Green dye, a bright green colour was seen in B. subtilis strains, while a brick-red colour was observed in negative control samples by visualizing under a UV transilluminator. The qPCR assay showed specific amplifications with a Ct value of 12 for B. subtilis strains and no amplification in negative control samples. In the sensitivity test, PCR could amplify DNA of B. subtilis up to 500 pg/μL. DNA concentration as low as 10 pg/μL was enough to show the colour change in the LAMP as well as the RPA assays, whereas the qPCR assay showed sensitivity till 100 pg/μL. All four diagnostic assays developed in the study have been validated in soil samples and B. subtilis-based biopesticides. Compared to conventional PCR, the qPCR assay has the advantage of quantification and visualizing the result in real-time, whereas LAMP and RPA assays have the benefits of being colourimetric and less time-consuming. The other advantages are that the results can be visualized with the naked eye, and these assays do not require a costly thermal cycler and gel documentation system. Hence, LAMP and RPA assays are highly suitable for developing point-of-need diagnostic kits and, in turn, help regulators assess the quality of biopesticides in the market.

• MeSH
• alkoholoxidoreduktasy * genetika   MeSH
• Bacillus subtilis * genetika   izolace a purifikace   enzymologie   MeSH
• bakteriální proteiny genetika   MeSH
• diagnostické techniky molekulární * metody   MeSH
• kolorimetrie * metody   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• půdní mikrobiologie MeSH
• senzitivita a specificita MeSH
• techniky amplifikace nukleových kyselin * metody   MeSH
• Publikační typ
• časopisecké články MeSH

Cíl: Používání filtroventrilačních systémů v městských autobusech ve vyspělých zemích zvyšuje komfort a kvalitu vnitřního ovzduší v prostředcích pozemní dopravy. Mikrobiální kontaminace byla studována na výstupních a vstupních plochách 5 vzduchových filtrů vyjmutých z klimatizačního systému městských autobusů při pravidelné údržbě. Materiál a metodika: K získání vzorků z výstupní i vstupní strany filtrů byla použita technika suchého stěru. Kultivace byla provedena na různých selektivních nebo selektivně-diagnostických půdách pro kultivaci životaschopných bakterií. K identifikaci bakteriálních druhů bylo použito barvení podle Grama a imerzní mikroskopie. Vybrané kolonie byly rovněž podrobeny proteomické studii. Po identifikaci byly bakterie kvantifikovány. Výsledky: Na vstupním i výstupním povrchu filtrů převažovaly bakterie rodu Bacillus – Bacillus cereus, Bacillus subtilis, Bacillus licheniformis, Bacillus pumilus, Bacillus flexus. Identifikovány byli také bakterie rodů Staphylococcus, Brevibacillus, Peribacillus a Paenibacillus. Kvantifikace ukázala nízkou kontaminaci výstupních povrchů filtrů 1 a 2. Kontaminace vstupní a výstupní strany filtrů 3, 4 a 5 a odhalila téměř stejnou kontaminaci vstupních a výstupních ploch. Závěry: Podle nalezených výsledků doporučujeme buď častější výměnu filtrů, nebo volbu filtrů s nižší porozitou.

The use of HVAC in urban buses in developed countries increases the comfort and indoor air quality in the means of ground transportation. The microbial contamination was studied on outlet and inlet surfaces of 5 air filters removed from the urban buses HVAC during regular maintenance. To acquire samples from both the outlet and the inlet sides of the filters, dry swabbing technique was used. Cultivation was performed on different selective or selective-diagnostic agars, to cultivate viable bacteria. To identify the bacterial species, Gram stain and immerse microscopy was used. Selected colonies underwent the proteomic study (MALDI-TOF) as well. After identification, bacteria were quantified. The bacteria of the genus Bacillus – Bacillus cereus, Bacillus subtilis, Bacillus licheniformis, Bacillus pumilus, Bacillus flexus prevailed on both inlet and outlet surfaces of the filters. The members of genera Staphylococcus, Brevibacillus, Peribacillus or Paenibacillus were also identified. The quantification of colony forming units showed low contamination of the outlet surfaces of filters 1 and 2. The contamination of inlet and outlet sides of filters 3, 4, and 5 was comparable, revealed nearly the same contamination of inlet and outlet surfaces. In the case of filters 3, 4 and 5 we recommend more frequent filter changing or more efficient filter choice.

Preterm prelabour rupture of membranes (PPROM) complicated by intra-amniotic inflammation (IAI) represents a substantial proportion of preterm birth cases. Currently, IAI is frequently defined as amniotic fluid IL-6 concentration above 2,600 pg/mL. However, the amniotic fluid IL-6 concentration was never correlated with the global response of other proinflammatory proteins to the ongoing IAI. In this cross-sectional study, protein quantification was performed using mass spectrometry (MS) analysis followed by target quantification of selected proinflammatory proteins. Levels of amniotic fluid proteins determined by MS were put into the correlation with IL-6 concentration determined by electrochemiluminescence immunoassay method (ECLIA). In total, 925 proteins were efficiently quantified and differential expression analysis revealed 378 proteins upregulated towards IL-6 concentration above 10,000 pg/mL. Four proteins (LCN2, MMP8, MPO, and S100A12) were selected to verify the achieved results and IL-6 concentration of 10,000 pg/mL was determined as the cut-off value for global IAI response.

• MeSH
• biologické markery metabolismus   MeSH
• chorioamnionitida * metabolismus   MeSH
• dospělí MeSH
• interleukin-6 metabolismus   MeSH
• lidé MeSH
• plodová voda * metabolismus   MeSH
• předčasný odtok plodové vody * metabolismus   patologie   MeSH
• protein S100A12 metabolismus   MeSH
• průřezové studie MeSH
• těhotenství MeSH
• zánět * metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

80letá pacientka s diabetem 2. typu byla pro neuspokojivou kompenzaci a symptomy hypoglykemie převedena z inzulínového režimu bazál-bolus s úspěchem na terapii IDegLira. Glykovaný hemoglobin se snížil ze 76 na 59 mmol/mol, příznaky hypoglykemie se neopakovaly, tělesná hmotnost se snížila z 88 na 82 kg. Celková pohoda a vitalita se zlepšily. Podmínkou úspěšné změny terapie byla kvantifikace postprandiální inzulínové sekrece (C-peptid nalačno 644,8 pmol/l, postprandiálně 1 782,2 pmol/l). Kazuistika dokládá pozitivní dopad změny terapie s využitím fixní kombinace dlouhodobě účinného inzulínového analoga degludek a liraglutidu (IDegLira) na kompenzaci diabetu, snížení rizika hypoglykemie a zlepšení životní pohody.

An 80-year-old female patient with type 2 diabetes was transferred, due to unsatisfactory diabetes control and hypoglycaemia symptoms, from basal-bolus insulin regimen to IDegLira therapy with success. Glycated haemoglobin was reduced from 76 to 59 mmol/mol, body weight was reduced from 88 to 82 kg, and hypoglycaemia symptoms did not recur. Overall well-being and vitality improved. The condition for a successful change in therapy was the quantification of postprandial insulin secretion (fasting C-peptide 644.8 pmol/l, postprandial 1,782.2 pmol/l). The case report proves the positive effect of therapy using a fixed combination of long-lasting insulin analogue degludec and liraglutide (IDegLira) on diabetes control, reducing the risk of hypoglycaemia and improvement of overall well-being.

Proteomics is nowadays increasingly becoming part of the routine clinical practice of diagnostic laboratories, especially due to the advent of advanced mass spectrometry techniques. This review focuses on the application of proteomic analysis in the identification of pathological conditions in a hospital setting, with a particular focus on the analysis of protein biomarkers. In particular, the main purpose of the review is to highlight the challenges associated with the identification of specific disease-causing proteins, given their complex nature and the variety of posttranslational modifications (PTMs) they can undergo. PTMs, such as phosphorylation and glycosylation, play critical roles in protein function but can also lead to diseases if dysregulated. Proteomics plays an important role especially in various medical fields ranging from cardiology, internal medicine to hemato-oncology emphasizing the interdisciplinary nature of this field. Traditional methods such as electrophoretic or immunochemical methods have been mainstay in protein detection; however, these techniques are limited in terms of specificity and sensitivity. Examples include the diagnosis of multiple myeloma and the detection of its specific protein or amyloidosis, which relies heavily on these conventional methods, which sometimes lead to false positives or inadequate disease monitoring. Mass spectrometry in this respect emerges as a superior alternative, providing high sensitivity and specificity in the detection and quantification of specific protein sequences. This technique is particularly beneficial for monitoring minimal residual disease (MRD) in the diagnosis of multiple myeloma where traditional methods fall short. Furthermore mass spectrometry can provide precise typing of amyloid proteins, which is crucial for the appropriate treatment of amyloidosis. This review summarizes the opportunities for proteomic determination using mass spectrometry between 2012 and 2024, highlighting the transformative potential of mass spectrometry in clinical proteomics and encouraging its wider use in diagnostic laboratories.

• MeSH
• amyloidóza * diagnóza   MeSH
• biologické markery analýza   MeSH
• hmotnostní spektrometrie * metody   MeSH
• lidé MeSH
• mnohočetný myelom * diagnóza   MeSH
• posttranslační úpravy proteinů MeSH
• proteomika * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Multidimensional chromatography coupled to tandem mass spectrometry (MS/MS), including simple sample preparation with protein precipitation, anion conversion with ammonium hydroxide, and solid-phase extraction using mixed-mode anion exchange in a 96-well plate format, has been validated for rapid simultaneous analysis of human insulin and its six analogs (lispro, glulisine, glargine, degludec, detemir, and aspart) in human plasma. This method is critical for clinical diagnostics, forensic investigations, and anti-doping efforts due to the widespread use of these substances. In the present study, improved chromatographic resolution was achieved using a first-dimension trap-and-elute configuration with an XBridge C18 (2.1 × 20 mm, 3.5 μm) trap column combined with second dimension separation on a Cortecs Ultra-High-Performance Liquid Chromatography (UHPLC) C18+ (2.1 × 100 mm, 1.6 μm) analytical column implemented within a two-dimensional-LC-MS/MS system. The total chromatographic run time was 11 min. This setup increases both the resolution and sensitivity of the method. A mobile phase consisting of 0.8% formic acid (FA) in water and 0.7% FA in acetonitrile was used for gradient elution. Bovine insulin was used as the internal standard. MS detection was performed in positive electrospray ionization mode, and the ion suppression due to matrix effects was evaluated. Validation criteria included linearity, precision, accuracy, recovery, lower limit of quantitation, matrix effect, and stability tests with and without protease inhibitor cocktail under different conditions (short-term stability, long-term stability, and freeze-thaw stability). The concentration range for all insulins was 50-15 000 pg/mL, with limits of quantification below the therapeutic reference range for all analytes. Intra-run precision ranged from 1.1% to 5.7%, inter-run precision from 0.7% to 5.9%, and overall recovery from 96.9% to 114.3%. The validated method has been implemented successfully by the Department of Forensic Medicine at our hospital for the investigation of unexplained deaths.

• MeSH
• chromatografie s reverzní fází * MeSH
• extrakce na pevné fázi MeSH
• inzulin * krev   analogy a deriváty   MeSH
• lidé MeSH
• tandemová hmotnostní spektrometrie * metody   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH